Eplerenona Pentafarma Adverse Reactions

Clinical Trial Adverse Events: Because clinical trials are conducted under very specific conditions the adverse drug reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.
NYHA Class II Chronic Heart Failure: EMPHASIS-HF study: NYHA Class II chronic heart failure: In the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF), safety was evaluated in 1364 patients treated with eplerenone and followed-up for a median duration of 675 days, and 1372 placebo-treated patients, followed-up for a median of 615 days during the double-blind phase of the trial. All causality adverse events that occurred in ≥2% of subjects treated with eplerenone (also incidence higher than placebo) are presented in Table 2. (See Table 2.)

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The overall incidence of treatment-related adverse events reported with eplerenone versus placebo was 21.3% and 17.1%, respectively. The only treatment-related AE that occurred in ≥2% of subjects in either treatment group was hyperkalemia (7.0% in the eplerenone group vs 2.9% in the placebo group). A total of 1272 subjects reported serious adverse events (SAE); 586 subjects (43.0%) in the eplerenone group and 686 subjects (50.0%) in the placebo group.
A total of 472 subjects discontinued from the study due to adverse events; 215 subjects (15.8%) in the eplerenone group and 257 subjects (18.7%) in the placebo group. A total of 32 subjects discontinued due to hyperkalemia; 19 subjects (1.4%) in the eplerenone group and 13 subjects (0.9%) in the placebo group.
A summary of the incidence of hyperkalemia and hypokalemia is provided in Table 5.
Heart Failure following Myocardial Infarction: EPHESUS study: Post-myocardial infarction heart failure: In the eplerenone post-acute myocardial infarction heart failure efficacy and survival study (EPHESUS), safety was evaluated in 3307 patients treated with eplerenone and 3301 placebo-treated patients. Patients were followed for an average of 16 months. Vital status was confirmed for 99.7% of patients.
The most serious adverse events in EPHESUS were endpoint events (e.g., death, cardiac failure) and these were significantly more frequent in the placebo treatment group. Serious adverse events that were significantly associated with eplerenone treatment included dehydration, arterial leg thrombosis, increased creatinine, and pyelonephritis; the incidence of these was low (≤0.5%).
Headache was the most frequent adverse reaction among eplerenone subjects in single- and multiple-dose trials. Adverse events that occurred more frequently in patients treated with eplerenone than placebo were hyperkalemia (summarized in Table 7). Eplerenone-treated patients also experienced more postural hypotension (0.7% vs 0.3% on placebo). Other adverse events more frequent during eplerenone treatment were increased blood urea nitrogen (BUN), increased creatinine, hypothyroidism, gastroesophageal reflux, pancreatitis, ketosis, arterial leg thrombosis, sepsis, and varicose veins. Hypokalemia (<3.5 mmol/l) occurred less frequently in patients treated with eplerenone (8.4% vs. 13.1%).
Elevation of serum potassium led to appropriate dose adjustments of eplerenone (see Table 1 in Dosage & Administration). Permanent discontinuations of eplerenone treatment due to hyperkalemia were infrequent (0.7% eplerenone vs 0.3% placebo); no eplerenone patient died from hyperkalemia. Sepsis led to permanent discontinuation of study medication in 2 eplerenone patients. No patients permanently discontinued study medication due to postural hypotension.
Adverse events experienced by ≥2.0% of subjects treated with eplerenone (also incidence higher than placebo) are presented in Table 3. (See Table 3.)

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The incidences of sex hormone-related adverse events are shown in Table 4. (See Table 4.)

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Clinical Chemistry Findings: EMPHASIS-HF study: NYHA Class II chronic heart failure: A summary of the incidence of hyperkalemia and hypokalemia is provided in Table 5. (See Table 5.)

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The higher risk of hyperkalemia in patients with renal impairment and, low estimated glomerular filtration rate (eGFR) and history of diabetes mellitus (EMPHASIS-HF study) are shown in Table 6 and Table 7 respectively. (See Tables 6 and 7.)

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EPHESUS study: Post-myocardial infarction heart failure: A summary of the incidence of hyperkalemia and hypokalemia is provided in Table 8. (See Table 8.)

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The higher risk of hyperkalemia in patients with renal impairment and, proteinuria and history of diabetes mellitus (EPHESUS study) are shown in Table 9 and Table 10 respectively. (See Tables 9 and 10.)

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Creatinine: Increases of more than 44 μmol/L were reported in 6.5% of patients administered eplerenone and in 4.9% of placebo-treated patients.
Blood Urea Nitrogen: In EPHESUS, a mean increase of 0.17 mmol/L in blood urea nitrogen (BUN) was reported in patients treated with eplerenone and a mean 0.31 mmol/L decrease for placebo-treated patients. BUN increased in 1.6% and 1.0% of subjects, respectively. The incidence of patients with a value of 1.3xULN for BUN is 36.0% for the eplerenone group compared to 30.5% for placebo.
Less Common Clinical Trial Adverse Events: EMPHASIS-HF study: NYHA Class II chronic heart failure: See Table 11.

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EPHESUS study: Post-myocardial infarction heart failure: See Table 12.

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